Issue 1 2008

Size does matter: macro ncRNAs and the regulation of imprinted gene clusters

Issue 1 2008 / 23 January 2008 /

The availability of the human and the mouse sequence has allowed genome-wide analysis of transcription to produce ‘transcriptomes’ that list all RNA transcripts in specific cell types or tissues. These studies have identified a surprisingly large number of ncRNAs that were not recognised by gene annotation programs applied to the genomic sequence. The earliest mouse transcriptome based on sequence annotation of full-length cDNA clones demonstrated that more than 70% of mapped cDNAs arose from non-coding transcripts and 15% of all transcripts formed sense/antisense pairs1. This surprising finding has been confirmed by genomic tiling arrays that allow whole chromosomes or genomes to be simultaneously analysed at a high resolution1-6 and showed that ncRNA transcripts constitutes the bulk of the mammalian transcriptome. To date, studies that quantify non-coding transcription have been performed in most model organisms7. Non-coding transcription is more prominent in higher eukaryotes, indicating that higher genome complexity made it necessary to make use of an additional layer of gene regulation. It should be noted that a recent yeast study showed that some antisense transcription might be an artefact arising from spurious synthesis of second-strand cDNA during reverse transcription reactions8. This indicates the amount of antisense non-coding transcription identified using strategies that did not include Actinomycin D may have been overestimated. (more…)

Tagged with: Denise P. Barlow, Functional genomics, macro ncRNAs, Paulina Latos, Stefan H. Stricker

Proteomics in the pharmaceutical industry: is the analytical challenge just too large?

Issue 1 2008 / 23 January 2008 /

Large scale techniques, such as combinatorial chemistry, high throughput screening and the various “omics” techniques, have largely entered the pharmaceutical and diagnosis industry besides the more classical and targeted approaches. Among these large scale techniques, proteomics is one for which there seems to be a widening gap between what is expected and what has been delivered to date, resulting in a strong questioning of the position and usefulness of proteomics in this industry.

The goal of this paper is to recall the strengths and weaknesses of proteomics, and to put them in perspective, so that more realistic expectations can be put forward. This can also lead to a more efficient rationale in implementing successful strategies in which proteomics will fully deliver.

The pharmaceutical and diagnosis industry is engaged in an ever-going race toward new molecules acting on new targets and/or new markers allowing a better diagnosis, prognosis or risk assessment. In this race, where time is a lot of money, heavily parallel screening is becoming increasingly important, as shown by the examples of high throughput screening and combinatorial synthesis. Within this frame of thinking, it is no wonder that proteomics, which can be defined as the large scale screening of proteins, has fostered a deep interest of the pharmaceutical industry in the last few years. However, there seems to be more and more voices stating that proteomics has not delivered what it promised, in other words that there is not enough bang for the bucks. (more…)

Tagged with: Proteomics, Thierry Rabilloud PhD

Genome-wide High Content Analysis of cellular pathways

Issue 1 2008 / 23 January 2008 /

Creating the molecular tools to combat human disease and infection remains the cornerstone activity of the pharmaceutical industry. The methodologies employed to discover new drugs has continually evolved as new biological techniques have emerged1; nevertheless the development of each novel compound is still only realised after many years of careful research, and a detailed analysis of its specific target.

These targets can potentially be any class of protein, and their selection is dependent on gathering sufficient high quality data about the pathway and reactions in which they are involved. The cataloguing of genes, and therefore proteins, that has come from genome-wide sequencing efforts now provides a resource from which new drug targets can be identified; however, the challenge is first to assign each of these genes to a particular pathway and function. One approach that can help achieve this is the use of microscopy-based assays in cultured cells. Cell-based assays are now well established in chemical compound screening to identify molecules affecting particular pathways2, but this does not globally address gene function. However, if cell-based assays are combined with protein over-expression or down-regulation approaches, gene function can be probed. Subsequent high content analysis (HCA) of the cells after such treatments can then provide quantitative and contextual information about the role of every gene in a particular pathway. This review will highlight some of the issues faced by researchers now employing this strategy. (more…)

Tagged with: Cellular Pathways, European Molecular Biology Laboratory (EMBL), HCS (High Content Screening), Jeremy C. Simpson

High throughput materials discovery “reducing product time to market”

Issue 1 2008 / 23 January 2008 /

With ever mounting market pressure on industries, from increasing global competition, along with consumer desire for value for money and improved performance results there is a greater driving force to stay one step ahead by reducing product time to market. This enforced impetus has many companies having to continually improve existing formulations and launch new products in order to expand their product portfolio and market share.

Although the use of automation to accelerate product development and reduce research bottle-necks is already well established in the pharmaceutical, bio-technology and catalysis industries, Automation in many other large industries, especially in the area of materials research, is still largely under-utilised and many processes are still performed manually.

There are a great number of benefits from using high throughput equipment and research methodologies to an organisation that chooses to implement them. The more apparent advantages are accelerated sample throughput, leading to reduced project time and cost which enables companies to compete more efficiently. It also provides the opportunity to map out a larger experimental space than possible with manual approaches, allowing the organisation to tackle research tasks previously thought to be beyond their capabilities and therefore letting them broaden their product patent coverage. Also, one of the less acknowledged benefits of the use of high throughput techniques is the “faster-to-no” result which allows companies to perform more speculative research and to rapidly identify and terminate unsuccessful projects. (more…)

Tagged with: Dr. Neil Campbell, Drug discovery, Lab Automation, University of Liverpool

Microbiology / Microbiologists – Where next?

Issue 1 2008 / 23 January 2008 /

Arguably microbiology is the oldest of the applied sciences, although early exponents doubtless had no understanding of how the fruits of their labour in fermentation for example, came about. The true forerunners of microbiology as it is recognised today would be Koch, Pasteur, Petri et al, who developed much of our basic understanding of the subject and many of the methods that are still in use approximately 150 years later. In that intervening period our knowledge of human and microbial genetics has dramatically increased and our exploitation of that knowledge has led to the current explosive growth of Biotechnology, such that clinically important biopharmaceuticals can now be produced by insect, plant, bacterial or mammalian cell lines or indeed in the milk of bovines.

But what of microbiology and microbiologists? If Pasteur or Koch were to return today, other than GCLP (Good Control Laboratory Practice) requirements which would be alien to them, they would still recognise the techniques being used to identify and enumerate micro-organisms in many pharmaceutical microbiological laboratories. Whilst there will probably always be a place for these traditional methods, microbiology/microbiologists must adapt to the changes in the industry. After all, in the space of 50 years or so, their chemistry colleagues have moved from thin layer chromatography and large hand packed column chromatography, to totally automated high pressure liquid chromatography and from calculating relative peak areas, by cutting out and weighing the graph paper to computerised integration! (more…)

Tagged with: Microbiology, Pharmig, Stewart Green

Trends in pharmaceutical cleanroom technology

Issue 1 2008 / 23 January 2008 /

There are many trends worth reporting in the context of pharmaceutical cleanroom technology: technical as well as regulatory trends. Supporting them is the continuing trend towards worldwide international standards, not only regarding contamination and biocontamination technology, but also regarding related topics such as air filtration. The endeavours for controlling micro-organisms, so competently addressed by the pharmaceutical industry and cleanroom technology, are beginning to spread – and this again is a trend – into further areas of human endeavour such as hospital hygiene. (more…)

Tagged with: Cleanrooms, Dr. Hans Schicht Ltd, Dr. sc. Techn, Hans H. Schicht

PQLI – providing practical solutions

Issue 1 2008 / 23 January 2008 /

This article discusses ISPE’s Product Quality Lifecycle Implementation (PQLI) initiative, which is to provide practical guidance for implementation of ICH Q8, Q9 and Q10. It represents the author’s individual opinion. It should be noted that PQLI is an evolving work area and so will continue to develop beyond the position explained at the time of writing this article. (more…)

Tagged with: Bruce Davis, PAT, Product Quality Lifecycle Implementation (PQLI)

PAT: a comprehensive guide

Issue 1 2008 / 23 January 2008 /

European Pharmaceutical Review presents a comprehensive guide to PAT addressing the challenges and advancements that are impacting upon PAT implementation in 2008 and beyond. (more…)

Tagged with: ABB, Ametek Process Instruments, Chris Hobbs, Eli Lilly, General Electric Analytical Instruments, Hach Ultra; Petter Mörée, Ingrid Maes, Matthew Smith, MKS Umetrics, PAT, Richard Godec, Siemens, Steven Doherty, Tony Slapikas